Program Director/Principal Investigator (Last, First, Middle): Bais, Harsh P. 1 R21 AI073323-01A1 ABSTRACT The research outlined in this grant proposes the development of an alternative therapeutic approach to treat Enterococcus infections. An important characteristic of this genus of bacteria is their resistance towards chemical and physical stress also, in contrast to other faecal bacteria that are released into the environment e.g. Escherichia coli, E. faecalis and E. faecium can survive for long periods outside their natural intestinal hosts. The E. faecalis and E. faecium are frequently associated with nosocomial infections (i.e. acquired in the hospital setting) and are resistant to almost all of the modern-age antibiotics. The proposed screening model involving plant root exudates presents a novel source for isolation of compounds that attenuate E. faecalis'and E. faecium's virulence and could potentially serve as an alternative approach to treat E. faecalis and E. faecium infections by discovering novel anti-infectives. The specific aims are Aim 1: To apply a whole plant screening method to test Enterococcus species pathogenicity. Identify plant species that reveal a tolerant phenotype in the in vitro based infections. Characterize the root secretions of the tolerant species against Enterococcus species. Test the anti-infective (virulence factors) activity of the tolerant root exudates in the nematode assays. Aim 2: To characterize compound(s) from the root exudates of tolerant plant species that exhibit antiinfective properties against Enterococcus species. To use classical nematode infection assays to characterize the effectiveness of the identified compound as an anti-infective agent. It is expected that these novel efforts will lead to the development of new therapeutics leading to characterization of anti-infective for the treatment of Enterococcus infections.